Study Details New Way to Measure Millisecond Changes in Brain Function

Sam Patz

The speed of the human brain is remarkable — in a fraction of a second, neurons are activated, triggering thoughts and reactions to stimuli like sound or light. The speed at which we can noninvasively follow brain function using an MRI has not been as impressive, but a team of Brigham investigators hopes to change that.

An existing MRI method to measure brain function is known as functional MRI (fMRI) and is based on detecting changes in blood oxygen levels. While fMRI has revolutionized the field of neuroscience by showing which specific areas of the brain “light up” during different brain tasks, the changes that fMRI is sensitive to can take up to six seconds to be visible in humans — practically an eon in brain time.

Brigham investigators, in collaboration with colleagues at King’s College London and INSERM-Paris, have discovered a fundamentally new way to measure brain function using a technology known as magnetic resonance elastography (MRE), an approach that creates maps of tissue stiffness using an MRI scanner. In a recent paper published in Science Advances, the team presented data from preclinical studies indicating that the technique can track brain function activity on a time scale of 100 milliseconds. Studies of the technique in human participants are now underway.

“What excites me most is that this is an entirely new method, and I’ve always been intrigued by new science,” said co-corresponding author and physicist Sam Patz, PhD, director of the Low Field and Pulmonary MRI laboratories in the Department of Radiology.

Following the Clues

This work, which started out as a hunch and is now being borne out by rigorous experiments, represents the culmination of a five-year collaboration of an international team dedicated to the pursuit of this new way of imaging brain function.

Among those with whom Patz worked closely was co-corresponding author Ralph Sinkus, PhD, a physicist and professor at King’s College London and INSERM-Paris. A pioneer in the field of MRE, Sinkus played a key role in helping to launch the MRE research program for preclinical testing in Patz’s Boston-based lab and in carrying out the latest research. Both scientists point to each other as an example of how a true collaborative relationship should function.

Although Patz was initially interested in applying MRE to the lungs, the team decided to begin by scanning the brain. Their results revealed something surprising: The tissue in the brain’s auditory cortex, which processes sound, was stiffening for no apparent reason.

“These results were so unexpected that we had to pursue them, and this observation is what sparked everything else,” Sinkus said.

On a hunch, Patz plugged one of the mouse’s ear canals with a gel. Sure enough, when he took another image, he saw the auditory cortex on the side of the brain that processed sound from that ear had begun to soften.

After this initial observation, the team spent more than a year modifying and improving both the MRE apparatus as well as the software to control the MRI scanner — both with the intent of improving the quality of the scans as well as designing a protocol to deal with issues they knew would be of concern to their colleagues. Then, with the new hardware and software, they rigorously demonstrated in preclinical studies that regions of the brain known to be activated by the stimulus they chose did, in fact, change their stiffness upon applying the stimulus. Researchers agreed the changes allow one to “see the brain thinking” in almost real-time.

“The intriguing novelty of this approach is that the stiffening/softening of specific brain regions persists even when stimuli as short as 100 milliseconds are presented to the mouse,” said Patz.

Next Steps

The team is now interested in using MREs to observe similar activity in the human brain, which could have implications for diagnosing and understanding diseases in which neuron activity may be slowed, disrupted or rerouted, such as Alzheimer’s, dementia, multiple sclerosis or epilepsy.

The team’s approach uses novel hardware to induce vibrations in the brain — an essential part to measure brain stiffness via MRI. Patz likens the apparatus to holding an electric toothbrush against one’s head to create tiny mechanical waves that travel through the brain.

The researchers presented data showing that altering the stimulus influenced the location, phase and intensity of the elasticity changes seen in the brain, meaning that they can visualize regional responses in the brain as they unfold at high speed.

“We believe this will transform our ability to observe neuronal functional activity with implications for neurological pathologies,” said Patz.